Clinics in gastroenterology最新文献

Diarrhoea can, in principle, result from the stimulation of secretion, the inhibition of absorption, or both. In practice, it is the simultaneous stimulation of secretion and inhibition of absorption that has most frequently been observed. The majority of substances affecting the intestine fall into two categories, those stimulating secretion and inhibiting absorption and those having the opposite effects. It is therefore important to understand both the mechanisms of secretion and the mechanisms of absorption. In this chapter, the basic cellular mechanisms by which water and electrolytes are actively absorbed and secreted in the small and large intestine have been presented. The steps at which these mechanisms are thought to be regulated by one or all of the three potential intracellular mediators, cAMP, cGMP and Ca++, have been indicated. It is hoped that an understanding of these basic cellular mechanisms will aid in understanding the pathophysiological conditions of diarrhoea described in the following chapters.

Congenital chloride diarrhoea is an autosomal recessive disease characterized by life-long watery diarrhoea of prenatal onset with high faecal Cl- concentration. Seventy-nine patients have so far been reported. The basic defect involves the active Cl-/HCO3- exchange mechanism of the distal ileum and colon. The defect causes impaired absorption of Cl-, acidity of intestinal contents because of impaired excretion of HCO3-, and, secondarily, impaired Na+ absorption. Intra-uterine diarrhoea leads to hydramnios and often to premature birth. Unless adequately treated, most patients will die of hypo-electrolytaemic dehydration within the 1st few months of life. Some infants will survive in such a state, with severe alkalosis, hypochloraemia, hypokalaemia, and retarded growth and development. Their plasma renin and aldosterone concentrations will become grossly elevated, and pathological changes will develop in the kidneys. The diagnosis is established when faecal Cl- concentration exceeds 90 mmol/l after water and electrolyte deficits have been corrected. Congenital chloride diarrhoea should be treated with full oral replacement of the faecal losses of Cl-, Na+, K+, and water. This therapy will abolish all the secondary disorders, provide for normal growth and development, and prevent renal disease. Though this therapy does not abolish the diarrhoea, most children will become toilet trained at a normal age, their social adjustment will be unimpaired, and they will live a perfectly normal life.

The papilla of Vater, diminutive as it may be, forms the nidus for a variety of clinical disorders. Owing to its crucial location at the confluence of the bile and pancreatic ducts, many of these clinical disorders lead to an impedance to the flow of secretions from the liver and pancreas. Thus, most symptomatic papillary disorders present with a rather predictable and monotonous conglomeration of symptoms. The common clinical presentations of papillary disorders include abdominal pain, jaundice, fever, pruritus and pancreatitis. Rarely, gastrointestinal bleeding leading to anaemia and weight loss may also be observed. The advent of ERCP rekindled interest in diseases of the papilla. The major duodenal papilla is more accessible now than ever before. The endoscopist can visualize the papilla within minutes and take an appropriate tissue sample using different biopsy techniques. Definitive diagnosis is thus possible in most patients with papillary tumours. Along with ERCP, the miniaturization of a perfusion system with minimal compliance enabled us to accurately evaluate sphincter of Oddi (SO) dynamics. This in turn gave us a wealth of information on the physiology of the sphincter of Oddi. In addition, ERCP manometry led to a resurgence of interest in SO dysfunction, especially papillary stenosis. Several characteristic manometric abnormalities have been identified recently. Finally, the introduction of endoscopic sphincterotomy (ES), nearly a decade ago, opened a new chapter in the therapeutic approach towards papillary disorders. While the technique was initially applied in the management of common bile duct stones in postcholecystectomy patients who were high operative risks, the indications for ES steadily increased during the past decade. Experience over the years led us to be convinced that ES is equally effective in the management of a variety of papillary disorders, including choledochoduodenal fistula, choledochocele, papillary tumours and SO dysfunction. Most recently, other ancillary procedures such as endoprosthesis insertion have emerged as yet another useful therapeutic modality. Such internal biliary stents have been shown to be suitable in establishing biliary drainage in ampullary neoplasms when the operative approach is considered risky.